1-27551305-G-C

Position:

chr1-27551305-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001371928.1(AHDC1):c.811C>G(p.Pro271Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000545 in 1,611,608 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

AHDC1
NM_001371928.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

AHDC1 (HGNC:25230): (AT-hook DNA binding motif containing 1) This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]

AHDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035629869).

BP6

Variant 1-27551305-G-C is Benign according to our data. Variant chr1-27551305-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 445768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00301 (458/152260) while in subpopulation AFR AF= 0.0108 (447/41562). AF 95% confidence interval is 0.00993. There are 3 homozygotes in gnomad4. There are 213 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 458 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHDC1	NM_001371928.1 linkuse as main transcript	c.811C>G	p.Pro271Ala	missense_variant	8/9	ENST00000673934.1	NP_001358857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHDC1	ENST00000673934.1 linkuse as main transcript	c.811C>G	p.Pro271Ala	missense_variant	8/9		NM_001371928.1	ENSP00000501218	P1

Frequencies

GnomAD3 genomes

AF:

0.00300

AC:

457

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000783

AC:

192

AN:

245138

Hom.:

AF XY:

0.000538

AC XY:

AN XY:

133730

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.000756

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000288

AC:

420

AN:

1459348

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

186

AN XY:

725978

show subpopulations

Gnomad4 AFR exome

AF:

0.00995

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.00301

AC:

458

AN:

152260

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

213

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000893

Hom.:

Bravo

AF:

0.00352

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00111

AC:

134

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	AHDC1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 15, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Feb 15, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

T;T;T;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.0020

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.73

.;.;T;.;.

MetaRNN

Benign

0.0036

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N;N

MutationTaster

Benign

0.90

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.31

N;.;N;.;.

REVEL

Benign

0.076

Sift

Pathogenic

0.0

D;.;D;.;.

Sift4G

Benign

0.38

T;.;T;.;.

Polyphen

0.0010

B;B;B;B;B

Vest4

0.28

MVP

0.10

MPC

1.3

ClinPred

0.066

GERP RS

4.3

Varity_R

0.091

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over